石墨烯在骨组织工程中的应用
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摘要
背景:石墨烯具有良好的生物相容性和高机械强度,已在组织工程学中广泛应用。目的:综述石墨烯的一般性质、降解性能、生物相容性及在骨组织工程中的应用。方法:应用计算机检索CNKI数据库、PubMed数据库及Elsevier数据库的2000年1月至2018年4月发表的相关文献,检索词为"石墨烯,石墨烯衍生物,组织工程,骨组织工程;graphene,graphene derivatives,tissue engineering,bone tissue engineering"。通过阅读文题和摘要进行初步筛选,排除与文章主题不相关的文献,根据纳入标准和排除标准,最终纳入65篇文献进行结果分析。结果与结论:(1)石墨烯具有良好的生物相容性、可降解性,细胞毒性较弱,对细胞增殖无明显影响,可作为组织工程支架搭载细胞,使其在上面生长;(2)石墨烯及其衍生物能够促进间充质干细胞的生长和成骨分化,对于修复骨缺损和骨再生有明显的促进作用,能够应用于骨组织工程的研究;(3)石墨烯和其他聚合物、矿物质或金属结合后能够改善其性能,可进一步促进其成骨分化的能力。
BACKGROUND: Graphene has good biocompatibility and high mechanical strength, which has been widely used in tissue engineering.OBJECTIVE: To review the general properties, degraded properties, biocompatibility, and application of graphene in bone tissue engineering METHODS: A computer-based search of CNKI, PubMed, and Elsevier was performed for retrieving articles concerning the application of graphene in bone tissue engineering published from January 2000 to April 2018. The keywords were "grapheme, graphene derivatives, tissue engineering, bone tissue engineering" in Chinese and English, respectively. The preliminary screening was carried out by reading titles and abstracts, and according to inclusion and exclusion criteria, 65 articles were finally included for result analysis after removal of unrelated articles.RESULTS AND CONCLUSION:(1) Graphene has good biocompatibility, degradability, weak cytotoxicity, and has no obvious effect on cell proliferation. Therefore, graphene can be used as a tissue engineering scaffold to carry cells that can grow on the scaffold surface.(2) Graphene and its derivatives can promote the growth and osteogenic differentiation of mesenchymal stem cells, and have a significant role in the repair of bone defects and bone regeneration. Therefore, they can be applied in bone tissue engineering.(3) Graphene combined with other polymers, minerals or metals can improve their performance, and can further promote the osteogenic differentiation.
BACKGROUND: Graphene has good biocompatibility and high mechanical strength, which has been widely used in tissue engineering.OBJECTIVE: To review the general properties, degraded properties, biocompatibility, and application of graphene in bone tissue engineering METHODS: A computer-based search of CNKI, PubMed, and Elsevier was performed for retrieving articles concerning the application of graphene in bone tissue engineering published from January 2000 to April 2018. The keywords were "grapheme, graphene derivatives, tissue engineering, bone tissue engineering" in Chinese and English, respectively. The preliminary screening was carried out by reading titles and abstracts, and according to inclusion and exclusion criteria, 65 articles were finally included for result analysis after removal of unrelated articles.RESULTS AND CONCLUSION:(1) Graphene has good biocompatibility, degradability, weak cytotoxicity, and has no obvious effect on cell proliferation. Therefore, graphene can be used as a tissue engineering scaffold to carry cells that can grow on the scaffold surface.(2) Graphene and its derivatives can promote the growth and osteogenic differentiation of mesenchymal stem cells, and have a significant role in the repair of bone defects and bone regeneration. Therefore, they can be applied in bone tissue engineering.(3) Graphene combined with other polymers, minerals or metals can improve their performance, and can further promote the osteogenic differentiation.
引文
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[2]Novoselov KS,Geim AK,Morozov SV,et al.Electric field effect inatomically thin carbon films.Science.2004;306(5696):666-669.
[3]Lee C,Wei X,Kysar JW,et al.Measurement of the elastic properties and intrinsic strength of monolayer grapheme.Science.2008;321(5887):385-388.
[4]Balandin AA,Ghosh S,Bao W,et al.Superior thermal conductivityof single-layer grapheme.Nano Lett.2008;8(3):902-907.
[5]Zhang B,Wang Y,Zhai G,et al.Biomedical applications of thegraphenebased materials.Mater Sci Eng C.2016;61(8):953-964.
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[28]Liu Y,Chen T,Du F,et al.Single-Layer Graphene Enhances the Osteogenic Differentiation of Human Mesenchymal Stem Cells In Vitro and In Vivo.J Biomed Nanotechnol.2016;12(6):1270-1284.
[29]Kenry,Lee WC,Loh KP,et al.When stem cells meet graphene:Opportunities and challenges in regenerative medicine.Biomaterials.2018;155:236-250.
[30]Xie H,Cao T,Rodríguez-Lozano FJ,et al.Graphene for the development of the next-generation of biocomposites for dental and medical applications.Dent Mater.2017;33(7):765-774.
[31]Kumar S,Azam MD,Raj S,et al.3D scaffold alters cellular response to graphene in a polymer composite for orthopedic applications.JBiomed Mater Res B Appl Biomater.2015;104(4):732-749.
[32]Feng P,Peng S,Wu P,et al.A nano-sandwich construct built with graphenenanosheets and carbon nanotubes enhances mechanical properties of hydroxyapatite-polyetheretherketone scaffolds.Int J Nanomedicine.2016;28(6):3487-500.
[33]Kumar S,Raj S,Kolanthai E,et al.Chemical functionalization of graphene to augment stem cell osteogenesis and inhibit biofilm formation on polymer composites for orthopedic applications.Acs Appl Mater Interfaces.2015;7(5):3237-3252.
[34]Kumar S,Raj S,Sarkar K,et al.Engineering a multi-biofunctional composite using poly(ethylenimine)decorated graphene oxide for bone tissue regeneration.Nanoscale.2016;8(12):6820-6836.
[35]Duan S,Yang X,Mei F,et al.Enhanced osteogenic differentiation of mesenchymal stem cells on poly(L-lactide)nanofibrous scaffolds containing carbon nanomaterials.J Biomed Mater Res A.2015;103(4):1424-1435.
[36]Shao W,He J,Sang F,et al.Enhanced bone formation in electrospun poly(l-lactic-co-glycolic acid)-tussah silk fibroin ultrafine nanofiber scaffolds incorporated with graphene oxide.Mater SciEng C.2016;62(6):823-834.
[37]Lyu CQ,Lu JY,Cao CH,et al.Induction of osteogenic differentiation of human adipose-derived stem cells by a novel self-supporting graphene hydrogel film and the possible underlying mechanism.ACS Appl Mater Interfaces.2015;7(36):20245-20254.
[38]Nair M,Nancy D,Krishnan AG,et al.Graphene oxide nanoflakes incorporated gelatin-hydroxyapatite scaffolds enhance osteogenic differentiation of human mesenchymal stem cells.Nanotechnology.2015;26(16):1-10.
[39]Xie C,Lu X,Han L,et al.Biomimetic Mineralized Hierarchical Graphene Oxide/Chitosan Scaffolds with Adsorbability for Immobilization of Nanoparticles for Biomedical Applications.ACSAppl Mater Interfaces.2016;8(3):1707-1717.
[40]Xie Y,Li H,Zhang C,et al.Graphene-reinforced calcium silicate coatings for load-bearing implants.Biomed Mater.2014;9(2):1-7.
[41]Shie MY,Chiang WH,Chen IWP,et al.Synergistic acceleration in the osteogenic and angiogenic differentiation of human mesenchymal stem cells by calcium silicate-graphene composites.Mater Sci Eng C.2017;73(4):726-735.
[42]Saravanan S,Anjali C,Vairamani M,et al.Scaffolds containing chitosan,gelatin and graphene oxide for bone tissue regeneration in vitro and in vivo.Int J BiolMacromol.2017;104(Pt B):1975-1985.
[43]Zancanela DC,Sim?o AMS,Francisco CG,et al.Graphene oxide and titanium:synergistic effects on the biomineralization ability of osteoblast cultures.J Mater Sci Mater Med.2016;27(4):1-9.
[44]Ren N,Li J,QiuJ,et al.Growth and accelerated differentiation of mesenchymal stem cells on graphene-oxide-coated titanate with dexamethasone on surface of titanium implants.Dent Mater 2017;33(7):525-535.
[45]Zhang W,Chang Q,Xu L,et al.Graphene Oxide-Copper Nanocomposite-Coated Porous CaP Scaffold for Vascularized Bone Regeneration via Activation of Hif-1α.Adv Healthc Mater.2016;5(11):1299-1309.
[46]Kumar S,Chatterjee K.Strontium eluting graphene hybrid nanoparticles augment osteogenesis in a 3D tissue scaffold.Nanoscale.2014;7(5):2023-2033.
[47]Chen J,Zhang X,Cai H,et al.Osteogenic activity and antibacterial effect of zinc oxide/carboxylatedgraphene oxide nanocomposites:Preparation and in vitro evaluation.Colloids Surfaces B Biointerfaces.2016;147(6):397-407.
[48]Zhang S,Yang Q,Zhao W,et al.In vitro and in vivo biocompatibility and osteogenesis of graphene-reinforced nanohydroxyapatite polyamide66 ternary biocomposite as orthopedic implant material.Int J Nanomedicine.2016;11(7):3179-3189.
[49]Nayak TR,Andersen H,Makam VS,et al.Graphene for controlled and accelerated osteogenic differentiation of humanmesenchymal stem cells.ACS Nano.2011;5(6):4670-4678.
[50]Wang CH,Guo ZS,Pang F,et al.Effects of Graphene Modification on the Bioactivation of Polyethylene-Terephthalate-Based Artificial Ligaments.ACS Appl Mater Interfaces.2015;7(28):15263-15276.
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[2]Novoselov KS,Geim AK,Morozov SV,et al.Electric field effect inatomically thin carbon films.Science.2004;306(5696):666-669.
[3]Lee C,Wei X,Kysar JW,et al.Measurement of the elastic properties and intrinsic strength of monolayer grapheme.Science.2008;321(5887):385-388.
[4]Balandin AA,Ghosh S,Bao W,et al.Superior thermal conductivityof single-layer grapheme.Nano Lett.2008;8(3):902-907.
[5]Zhang B,Wang Y,Zhai G,et al.Biomedical applications of thegraphenebased materials.Mater Sci Eng C.2016;61(8):953-964.
[6]Holt BD,Wright ZM,Arnold AM,et al.Graphene oxide as a scaffold for bone regeneration.Wiley Interdiscip Rev Nanomed Nanobiotechnol.2017;9(3).doi:10.1002/wnan.1437.Epub 2016 Oct 26.
[7]Jafari M,Paknejad Z,Rad MR,et al.Polymeric scaffolds in tissue engineering:a literature review.J Biomed Mater Res B Appl Biomater.2017;105(2):431-459.
[8]Gong T,Xie J,Liao J,et al.Nanomaterials and bone regeneration.Bone Res.2015;3(3):123-129.
[9]吕成奇,邹德荣.石墨烯材料在组织工程方面应用的新进展[J].口腔医学,2014,34(4):304-306.
[10]Zhang Y,Ali SF,Dervishi E,et al.Cytotoxicity effects of graphene and single-wall carbon nanotubes in neural phaeochromocytomaderived PC12 cells.Acs Nano.2010;4(6):3181-3186.
[11]Kalbacova M,Broz A,Kong J,et al.Graphene substrates promoteadherence of human osteoblasts and mesenchymal stromal cells.Carbon.2010;48(15):4323-4329.
[12]徐宏杨,范敏敏,张志荣,等.氧化石墨烯PEG化后对L929细胞毒性的影响[J].华西药学杂志,2015,30(4):425-427.
[13]Liao KH,Lin YS,Macosko CW,et al.Cytotoxicity of graphene oxide and graphene in human erythrocytes and skin fibroblastsACSAppl Mater Interfaces.2011;3(7):2607-2615.
[14]赵梦,温朝辉.石墨烯及其复合材料在组织工程领域的研究进展[J].医学研究杂志,2017,46(12):175-178.
[15]Bengtson S,Kling K,Madsen AM,et al.No cytotoxicity or genotoxicity of graphene and graphene oxide in murine lung epithelial FE1 cells in vitro.Environ Mol Mutagen.2016;57(6):469-476.
[16]Girish CM,Sasidharan A,Gowd GS,et al.Confocal Raman imaging study showing macrophage mediated biodegradation of graphene in vivo.Adv Healthc Mater.2013;2(11):1489-1500.
[17]Schinwald A,Murphy F,Askounis A,et al.Minimal oxidation and inflammogenicity of pristine graphene with residence in the lung.Nanotoxicology.2014;8(8):824-832.
[18]Jin L,Lee JH,Jin OS,et al.Stimulated osteogenic differentiation of human mesenchymal stem cells by reduced graphene oxide.JNanosci Nanotechnol.2015;15(10):7966-7970.
[19]Kang ES,Kim DS,Suhito IR,et al.Guiding osteogenesis of mesenchymal stem cells using carbon-based nanomaterials.Nano Convergence.2017;4(1):1-14.
[20]Han X,Chua M,Islam I,et al.CVD-grown monolayer graphene induces osteogenic but not odontoblastic differentiation of dental pulp stem cells.Dent Mater.2016;33(1):13-21.
[21]Crowder SW,Prasai D,Rath R,et al.Three-dimensional graphene foams promote osteogenic differentiation of humanmesenchymal stem cells.Nanoscale.2013;5(10):4171-4176.
[22]Lee WC,Lim CH,Shi H,et al.Origin of enhanced stem cell growth and differentiation on graphene and graphene oxide.Acs Nano.2011;5(9):7334-7341.
[23]Aryaei A,Jayatissa AH,Jayasuriya AC,et al.The effect of graphene substrate on osteoblast cell adhesion and proliferation.J Biomed Mater Res A.2014;102(9):3282-3290.
[24]Elkhenany H,Amelse L,Lafont A,et al.Graphene supports in vitro proliferation and osteogenic differentiation of goat adult mesenchymal stem cells:potential for bone tissue engineering.JAppl Toxicol.2015;35(4):367-374.
[25]Lee WC,Lim CH,Shi H,et al.Origin of Enhanced Stem Cell Growth and Differentiation on Graphene and GrapheneOxide.Acs Nano.2011;5(9):7334-7341.
[26]Nayak TR,Andersen H,Makam VS,et al.Graphene for controlled and accelerated osteogenic differentiation of human mesenchymal stem cells.ACS Nano.2011;5(6):4670-4678.
[27]吕成奇,陆家瑜,于佳,等.自撑式石墨烯水凝胶诱导人脂肪干细胞成骨分化的体外研究[J].口腔医学,2014,34(7):486-491.
[28]Liu Y,Chen T,Du F,et al.Single-Layer Graphene Enhances the Osteogenic Differentiation of Human Mesenchymal Stem Cells In Vitro and In Vivo.J Biomed Nanotechnol.2016;12(6):1270-1284.
[29]Kenry,Lee WC,Loh KP,et al.When stem cells meet graphene:Opportunities and challenges in regenerative medicine.Biomaterials.2018;155:236-250.
[30]Xie H,Cao T,Rodríguez-Lozano FJ,et al.Graphene for the development of the next-generation of biocomposites for dental and medical applications.Dent Mater.2017;33(7):765-774.
[31]Kumar S,Azam MD,Raj S,et al.3D scaffold alters cellular response to graphene in a polymer composite for orthopedic applications.JBiomed Mater Res B Appl Biomater.2015;104(4):732-749.
[32]Feng P,Peng S,Wu P,et al.A nano-sandwich construct built with graphenenanosheets and carbon nanotubes enhances mechanical properties of hydroxyapatite-polyetheretherketone scaffolds.Int J Nanomedicine.2016;28(6):3487-500.
[33]Kumar S,Raj S,Kolanthai E,et al.Chemical functionalization of graphene to augment stem cell osteogenesis and inhibit biofilm formation on polymer composites for orthopedic applications.Acs Appl Mater Interfaces.2015;7(5):3237-3252.
[34]Kumar S,Raj S,Sarkar K,et al.Engineering a multi-biofunctional composite using poly(ethylenimine)decorated graphene oxide for bone tissue regeneration.Nanoscale.2016;8(12):6820-6836.
[35]Duan S,Yang X,Mei F,et al.Enhanced osteogenic differentiation of mesenchymal stem cells on poly(L-lactide)nanofibrous scaffolds containing carbon nanomaterials.J Biomed Mater Res A.2015;103(4):1424-1435.
[36]Shao W,He J,Sang F,et al.Enhanced bone formation in electrospun poly(l-lactic-co-glycolic acid)-tussah silk fibroin ultrafine nanofiber scaffolds incorporated with graphene oxide.Mater SciEng C.2016;62(6):823-834.
[37]Lyu CQ,Lu JY,Cao CH,et al.Induction of osteogenic differentiation of human adipose-derived stem cells by a novel self-supporting graphene hydrogel film and the possible underlying mechanism.ACS Appl Mater Interfaces.2015;7(36):20245-20254.
[38]Nair M,Nancy D,Krishnan AG,et al.Graphene oxide nanoflakes incorporated gelatin-hydroxyapatite scaffolds enhance osteogenic differentiation of human mesenchymal stem cells.Nanotechnology.2015;26(16):1-10.
[39]Xie C,Lu X,Han L,et al.Biomimetic Mineralized Hierarchical Graphene Oxide/Chitosan Scaffolds with Adsorbability for Immobilization of Nanoparticles for Biomedical Applications.ACSAppl Mater Interfaces.2016;8(3):1707-1717.
[40]Xie Y,Li H,Zhang C,et al.Graphene-reinforced calcium silicate coatings for load-bearing implants.Biomed Mater.2014;9(2):1-7.
[41]Shie MY,Chiang WH,Chen IWP,et al.Synergistic acceleration in the osteogenic and angiogenic differentiation of human mesenchymal stem cells by calcium silicate-graphene composites.Mater Sci Eng C.2017;73(4):726-735.
[42]Saravanan S,Anjali C,Vairamani M,et al.Scaffolds containing chitosan,gelatin and graphene oxide for bone tissue regeneration in vitro and in vivo.Int J BiolMacromol.2017;104(Pt B):1975-1985.
[43]Zancanela DC,Sim?o AMS,Francisco CG,et al.Graphene oxide and titanium:synergistic effects on the biomineralization ability of osteoblast cultures.J Mater Sci Mater Med.2016;27(4):1-9.
[44]Ren N,Li J,QiuJ,et al.Growth and accelerated differentiation of mesenchymal stem cells on graphene-oxide-coated titanate with dexamethasone on surface of titanium implants.Dent Mater 2017;33(7):525-535.
[45]Zhang W,Chang Q,Xu L,et al.Graphene Oxide-Copper Nanocomposite-Coated Porous CaP Scaffold for Vascularized Bone Regeneration via Activation of Hif-1α.Adv Healthc Mater.2016;5(11):1299-1309.
[46]Kumar S,Chatterjee K.Strontium eluting graphene hybrid nanoparticles augment osteogenesis in a 3D tissue scaffold.Nanoscale.2014;7(5):2023-2033.
[47]Chen J,Zhang X,Cai H,et al.Osteogenic activity and antibacterial effect of zinc oxide/carboxylatedgraphene oxide nanocomposites:Preparation and in vitro evaluation.Colloids Surfaces B Biointerfaces.2016;147(6):397-407.
[48]Zhang S,Yang Q,Zhao W,et al.In vitro and in vivo biocompatibility and osteogenesis of graphene-reinforced nanohydroxyapatite polyamide66 ternary biocomposite as orthopedic implant material.Int J Nanomedicine.2016;11(7):3179-3189.
[49]Nayak TR,Andersen H,Makam VS,et al.Graphene for controlled and accelerated osteogenic differentiation of humanmesenchymal stem cells.ACS Nano.2011;5(6):4670-4678.
[50]Wang CH,Guo ZS,Pang F,et al.Effects of Graphene Modification on the Bioactivation of Polyethylene-Terephthalate-Based Artificial Ligaments.ACS Appl Mater Interfaces.2015;7(28):15263-15276.
[51]Liu H,Cheng J,Chen F,et al.Gelatin functionalizedgraphene oxide for mineralizationof hydroxyapatite:biomimetic and in vitroevaluation.Nanoscale.2014;6(10):5315-5322.
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